title: The effects of midazolam and sevoflurane on the GABA(A) receptors with alternatively spliced variants of the γ2 subunit.
abstract: BACKGROUND
  Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABA(A) receptor changes with age. Therefore, we hypothesized that alternative splicing of the γ2 subunit affects the GABA current when applying sevoflurane and midazolam.
  
  
  METHODS
  We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with α1β2γ2L or α1β2γ2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 µM of GABA.
  
  
  RESULTS
  The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the α1β2γ2L and α1β2γ2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the α1β2γ2S subtype, but not for the α1β2γ2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes.
  
  
  CONCLUSIONS
  These results show that the difference in the γ2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the γ2 subunit and the concentration of both drugs.
authors.affiliation: Department of Anesthesiology and Pain Medicine, National Cancer Center, Goyang, Korea.
authors.forename: Woosik
authors.initials: W
authors.lastname: Eom
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Park
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Hee-Soo
authors.initials: HS
authors.lastname: Kim